GeroScience最新文献

{"title":"No effect of anodal high-definition transcranial direct current stimulation during motor sequence learning in older people.","authors":"Silke Kerstens, Sanne Broeder, Moran Gilat, Evelien Nackaerts, Britt Vandendoorent, Alice Nieuwboer, Jean-Jacques Orban de Xivry","doi":"10.1007/s11357-026-02457-8","DOIUrl":"10.1007/s11357-026-02457-8","url":null,"abstract":"<p><p>Transcranial direct current stimulation (tDCS) targeting the primary motor cortex (M1) has previously been shown to enhance motor learning in older adults. However, findings across studies are inconsistent, which may be partly due to variability in stimulation parameters and montages across experimental protocols. We aimed to replicate the effect of 1 mA conventional anodal tDCS over the M1 hotspot during one session of motor sequence learning on retention (24 h) compared to sham stimulation in older adults. In addition, we aimed to compare the effect of high definition (HD tDCS) versus conventional tDCS on motor sequence learning to explore if stimulation montage and according focality affects the effect sizes found. In a pre-registered, double-blind, randomized, sham-controlled, parallel study involving 52 older adults, we investigated the effects of conventional and HD tDCS on motor sequence learning using a serial reaction time task (SRTT). We employed a hybrid design, whereby the primary contrast (active stimulation vs. sham) was assessed using the parallel study framework, while a crossover design was embedded to compare the stimulation montage. Although all groups showed motor sequence learning over time, both during practice sessions (main effect of time: p < 0.0001), as well as across session (main effect of time: p < 0.0001), we observed no significant effects on learning between stimulation groups (main effect of stimulation: p = 0. 68) or montages (main effect of montage: p = 0. 66). For all groups, motor sequence learning improvements were maintained but not further enhanced after 24 h of consolidation (HD tDCS: p = 0.64; conventional tDCS: p = 0.76; HD sham: p = 0.69; conventional sham: p = 0.57). Our findings indicate that neither conventional nor HD tDCS enhanced motor sequence learning in older adults. To better understand potential long-term or cumulative effects, we recommend that future studies investigate the effects of repeated tDCS sessions administered throughout the motor learning process.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7545-7560"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psycho-socio-economic factors and risk of cardiorenal multimorbidity in middle to older-aged adults: prospective findings from the Canadian longitudinal study on aging.","authors":"Setor K Kunutsor, Reyhaneh Rikhtehgaran, Anita Soni","doi":"10.1007/s11357-025-02081-y","DOIUrl":"10.1007/s11357-025-02081-y","url":null,"abstract":"<p><p>Psycho-socio-economic factors (PSEFs) such as income and homeownership may influence the prevalence of cardiorenal multimorbidity (CRM), yet their prospective associations with CRM risk remain unclear. This study aimed to estimate CRM incidence and examine its relationships with multiple PSEFs in a nationally representative Canadian cohort. We analyzed data from 16,557 participants (mean age: 60.4 years; 48.9% men) in the Canadian Longitudinal Study on Aging (CLSA) who were free of CRM at baseline (2010-2015). Incident CRM was defined as the co-occurrence of at least one cardiovascular disease and kidney disease at second follow-up (2018-2021). Survey-weighted multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PSEFs and CRM risk. Over 3-11 years follow-up, 194 participants (1.2%) developed CRM, corresponding to 8.80 per 1,000 individuals (95% CI: 6.77-11.40). CRM incidence increased with age, was higher in men than women (10.63 vs. 7.35 per 1,000), urban than rural residents (9.69 vs. 3.72 per 1,000), and immigrants than non-immigrants (10.87 vs. 8.49 per 1,000). Greater tangible social support reduced CRM risk (OR = 0.65; 95% CI: 0.43-0.97), while depression (OR = 1.68; 95% CI: 1.07-2.65) and PTSD (OR = 3.14; 95% CI: 1.74-5.67) increased risk. In middle- to older-aged Canadian adults, higher social support appears protective, whereas depression and PTSD increase CRM risk. Although incidence was low, CRM burden rose with age and was higher among men, urban residents and immigrants. These findings highlight the importance of psychosocial well-being and social connectedness in preventing CRM and reducing multimorbidity burden in aging populations.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7707-7719"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTUPB improves cognitive function in Alzheimer's disease associated with enhancing cerebral vascular myogenic response and attenuating vascular remodeling.","authors":"Gilbert C Morgan, Andrew Gregory, Chengyun Tang, Sung Hee Hwang, Jane J Border, Jing Xu, Yedan Liu, Shan Bai, Tae Jin Lee, Cameron Cantwell, David Bunn, Karen M Wagner, Christophe Morisseau, Carly Pittman, Alina Ngo, Peter Osayi, Aditi Pabbidi, Philip O'Herron, Zsolt Bagi, Jessica A Filosa, Hongwei Yu, Cindy McReynolds, Bruce D Hammock, Richard J Roman, Fan Fan","doi":"10.1007/s11357-026-02140-y","DOIUrl":"10.1007/s11357-026-02140-y","url":null,"abstract":"<p><p>Genetic studies have linked EPHX2 (encoding soluble epoxide hydrolase, sEH) and PTGS2 (encoding cyclooxygenase-2, COX-2) to Alzheimer's disease (AD). Elevated levels of sEH and COX-2 found in AD patients and animals suggest their involvement in neurodegeneration, glial activation, vascular dysfunction, and inflammation. This study evaluated the effects of a new dual sEH/COX-2 inhibitor, PTUPB, on cerebrovascular function and cognition in TgF344-AD rats. The rats received oral PTUPB (2 mg/kg/day) for 25 days. Body weight, plasma glucose, and HbA1c levels remained stable between PTUPB- and vehicle-treated AD rats. PTUPB significantly improved recognition memory in AD rats, as detected by the novel object recognition test. Pressure myography showed that PTUPB restored myogenic responses and increased the distensibility of the middle cerebral arteries (MCAs) in AD rats. Acute PTUPB (0.1 and 1 μM) enhanced myogenic contraction in response to elevated perfusion pressure in AD MCAs, with minimal effects in wild-type vessels. Transcriptomic analysis of cerebral vascular smooth muscle cells from AD rats revealed that PTUPB influences genes involved in contractility, extracellular matrix remodeling, inflammation, and oxidative stress. These results provide new evidence that dual inhibition of sEH and COX-2 improves cognition in AD and is associated with enhanced myogenic response via attenuation of vascular remodeling. Our findings highlight the potential of PTUPB as a therapeutic approach for cerebrovascular dysfunction in AD.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8367-8383"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coordinated control of proteasome subunit gene expression promotes stress resistance, proteostasis, and longevity.","authors":"Irini Topalidou, Nicolas Lehrbach","doi":"10.1007/s11357-026-02146-6","DOIUrl":"10.1007/s11357-026-02146-6","url":null,"abstract":"<p><p>The proteasome is essential for cellular protein homeostasis through selective destruction of damaged and misfolded proteins. Failure of proteasome-dependent turnover accompanied by accumulation and aggregation of aberrant proteins is a hallmark of aging and late-onset neurodegenerative diseases. SKN-1A/Nrf1, a member of the NFE2L/Nrf family of transcription factors, is a master regulator of proteasome biogenesis. Through transcriptional control of proteasome subunit gene expression, SKN-1A/Nrf1 controls homoeostatic and stress-responsive upregulation of proteasome levels in adaptation to proteasome dysfunction or protein misfolding. SKN-1A/Nrf1 acts in concert with another Nrf family transcription factor, SKN-1C/Nrf2, to regulate many aspects of physiology including stress responses, redox balance, immunity, and metabolism. Here, we demonstrate that a small deletion in the promoter of the pbs-5 gene, which encodes an essential proteasome subunit, uncouples its expression from transcriptional regulation by SKN-1A/Nrf1. This disruption leads to compensatory SKN-1A/Nrf1-dependent upregulation of other proteasome subunit genes, resulting in a homeostatic imbalance in proteasomal gene expression. This pbs-5 regulatory mutation phenocopies some, but not all, aspects of SKN-1A/Nrf1 inactivation, providing evidence that coordinated regulation of proteasomal subunit gene expression underlies a subset of SKN-1A/Nrf1's physiological roles. In comparing the effects of the pbs-5 promoter deletion with isoform-specific inactivation of SKN-1A or SKN-1C, we show that the pbs-5 promoter mutation completely abrogates multiple lifespan extension paradigms. These results reveal that coordinated homeostatic regulation of proteasome subunit gene expression is critical for longevity and healthy aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8565-8589"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peucedanum japonicum Thunb. ameliorates age-related muscle loss by improving mitochondrial function in aged mice.","authors":"Young In Kim, Young-Soo Kim, Chang Hwa Jung, Jiyun Ahn","doi":"10.1007/s11357-026-02123-z","DOIUrl":"10.1007/s11357-026-02123-z","url":null,"abstract":"<p><p>Peucedanum japonicum Thunb. (PJ), also known as costal hog fennel, is an edible medicinal plant recognized for its potential health benefits. We previously demonstrated the protective effects of PJ against muscle atrophy in young mice. In the present study, we investigated whether PJ also inhibits age-related muscle loss in aged mice. PJ treatment of primary myoblasts derived from aged mice attenuated myotube diameter reduction, suppressed the expression of atrogenes, and prevented the fast-to-slow myosin heavy chain (MHC) fiber type transition. Additionally, PJ improved mitochondrial respiratory capacity, accompanied by increased PGC1α expression and phosphorylation. Aged mice (20 months old) were fed diets supplemented with 0.1% or 0.2% PJ for eight weeks. PJ supplementation enhanced muscle strength and physicalrformance parameters, including treadmill endurance and stride length. Increases in lean body mass, muscle weight, cross-sectional area (CSA), and the ratio of MHCII to MHCI fibers were observed. These improvements were associated with reduced ubiquitin-dependent protein degradation and the downregulation of atrogenes. Furthermore, PJ supplementation promoted mitochondrial activity via PGC1α and stimulated mitochondrial biogenesis through the Nrf1-Tfam pathway. 4-Caffeoylquinic acid (4-CQA), a major bioactive compound in PJ, attenuated myotube atrophy and enhanced mitochondrial respiration in aged myoblasts. These findings suggested that PJ, along with its active compound 4-CQA, has therapeutic potential for combating age-related muscle loss.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8505-8518"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with a selective androgen receptor modulator (RAD140) is linked to better cardiac function, with male-specific effects that are graded by interleukin-6.","authors":"Stefan S Heinze, David G Sapp, Alexander P Young, Susan E Howlett","doi":"10.1007/s11357-026-02151-9","DOIUrl":"10.1007/s11357-026-02151-9","url":null,"abstract":"<p><p>Low testosterone levels are associated with impaired cardiac function and elevated circulating inflammatory markers, which are mechanistically related. Selective androgen receptor (AR) modulators (SARMs) can stimulate ARs and mimic testosterone. Whether SARMs affect cardiac structure or function and if circulating inflammatory markers grade these changes is unclear. We investigated the effects of a SARM (RAD140) on cardiac function and structure in older male and female mice and explored how systemic inflammatory markers relate. Older (23-month-old) male and female mice were treated with RAD140 (5 mg/kg/day) for 6-weeks. Left ventricular (LV) structure and function were measured with echocardiography. Serum cytokine levels were assessed with a multiplex assay, and LV gene expression was tested. RAD140 treated males and females had higher ejection fraction (+ 10.4%), stroke volume (+ 9.6 µL) and cardiac output (+ 4.5 mL/min), versus controls. However, RAD140 treated males had better markers of cardiac function, including myocardial strain (-5.8%) and isovolumic relaxation times (-4.7 ms) compared to controls, with lesser or opposite effects in females. Higher levels of interleukin-6 correlated with worse global circumferential strain in males, but not females. qPCR analysis for genes coding proteins related to cardiac function and structure revealed no differences, although AR mRNA was lower with RAD140 treatment in both sexes. No structural differences were observed. RAD140 treatment may enhance cardiac function in older male mice, but less so in older female mice. Increased circumferential strain in males related to lower interleukin-6 levels, supporting the AR's connecting role between cardiac function and inflammatory markers.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8545-8563"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertension-associated DNA methylation signatures and multi-generational epigenetic clocks in Korean adults.","authors":"Jangho Lee, Soo-Hyun Park, Jin-Taek Hwang, Jae-Ho Park","doi":"10.1007/s11357-026-02433-2","DOIUrl":"10.1007/s11357-026-02433-2","url":null,"abstract":"<p><p>Hypertension is a hallmark of vascular aging; however, the epigenetic link between biological aging and blood pressure remains unclear. This epigenome-wide association study of hypertension examined 1528 Korean adults (896 normotensive, 632 hypertensive) from the Korean Genome and Epidemiology Study using the Illumina MethylationEPIC 850K array. Overall, 53 differentially methylated positions and 10 differentially methylated regions were identified, with the top region mapping to HIVEP3, an NF-kappaB signaling inhibitor. Among the twelve hallmarks of aging, only chronic inflammation showed nominal enrichment (OR = 23.13, P = 0.045); this signal was driven solely by HIVEP3 and did not retain significance after accounting for multiple hallmarks. All five epigenetic clocks spanning three generations were significantly associated with hypertension, and DunedinPACE showed the strongest statistical significance (per-standard-deviation OR = 1.51, P = 1.3 × 10^-8). Statistical mediation analysis revealed that all five clocks were consistent with mediating the age-hypertension association, with PC-GrimAge showing the largest proportion (62.2%) and DunedinPACE the most robust statistical significance (16.4%, P < 0.001). Machine-learning classification achieved an area under the curve of 0.910, with negligible improvement after the addition of epigenetic age features (+ 0.003), indicating substantial redundancy between hypertension-associated methylation sites and epigenetic age measures. Independent replication in 392 participants showed directional concordance for 64.7% of differentially methylated positions (P = 0.049). These exploratory findings indicate that hypertension-associated epigenetic changes are captured by multi-generational epigenetic clocks and may implicate inflammation-related pathways, warranting confirmation in longitudinal studies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7441-7455"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attentionally directed oculomotor training produces disease-stage-dependent effects on plasma tau, cognition, and oculomotor signatures in patients with mild cognitive impairment.","authors":"Ricardo Martínez-Flores, Laura Pérez Zapata, Marta Del Campo Milan, Helena Blasco-Forniés, Esther Jiménez-Moyano, Javier Torres-Torronteras, Marc Suárez-Calvet, Agustin Ibáñez, Isabel Martín-Sobrino, Neus Falgàs, Oriol Grau-Rivera, Carlos Cristi-Montero, Corinna Perone, Hans Supèr","doi":"10.1007/s11357-026-02474-7","DOIUrl":"10.1007/s11357-026-02474-7","url":null,"abstract":"<p><p>Attentionally directed oculomotor training may engage circuits implicated in gamma-band modulation and early Alzheimer's disease (AD) pathophysiology, yet its effects across mild cognitive impairment (MCI) risk strata remain unclear. We aimed to determine whether this training, delivered through a gamified eye-tracking task, is associated with differential effects on plasma neurodegeneration biomarkers, cognitive performance, and oculomotor signatures in individuals with MCI at differential risk of conversion to Alzheimer's dementia. Twenty-nine participants with MCI were stratified into MCI-HR (n = 17) and MCI-LR (n = 12) based on validated MoCA and MoCA-MIS cut-off scores and completed 8 weeks of daily oculomotor training. Outcomes were assessed pre/post using permutation tests, bootstrapped Hedges' g, and linear mixed-effects models. Cognitive performance improved in both groups (MoCA: g = 1.27-2.17; MoCA-MIS: g = 1.02-1.68), with no between-group difference. Plasma tau diverged by stratum: MCI-LR showed reductions in pTau-181 (g = -0.64, 95% CI [-1.07, -0.15]) and pTau-217 (g = -0.72, 95% CI [-1.08, -0.36]), whereas MCI-HR showed an increase in pTau-181 (g = 0.82, 95% CI [0.53, 1.16]; between-group g = 1.31, 95% CI [0.89, 1.78], p = 0.001). Amyloid, GFAP, and NfL remained stable. MCI-HR showed reduced accuracy and increased reaction times (+196.4 ms, p < 0.001); MCI-LR maintained stable performance. Oculomotor signatures diverged between strata post-training (group × time × stimulus interactions, p = 0.013-0.045). In MCI-LR, oculomotor changes correlated with reductions in pTau-181 (ρ = -0.60, 95% CI [-0.96, -0.20]) and pTau-217 (ρ = -0.69, 95% CI [-0.95, -0.20]). Oculomotor training produced stratum-dependent responses: biomarker reductions and oculomotor-molecular coupling in MCI-LR, and dissociated physiological and behavioral outcomes in MCI-HR, suggesting disease-stage-specific neuroplasticity capacity linked to tau-related processes.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7523-7544"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney function and all-cause mortality in the oldest-old population: a three-cohort longitudinal study.","authors":"Hideaki Kurata, Shu Meguro, Yukiko Abe, Takashi Sasaki, Yasumichi Arai, Nobuyoshi Hirose, Kaori Hayashi","doi":"10.1007/s11357-026-02130-0","DOIUrl":"10.1007/s11357-026-02130-0","url":null,"abstract":"<p><p>With increasing global life expectancy, the prognostic significance of kidney function in centenarians and supercentenarians should be clarified. The conventional estimated glomerular filtration rate (eGFR) threshold of < 60 mL/min/1.73 m² may not accurately reflect chronic kidney disease (CKD) in this population, highlighting the need for age-adapted definitions. This study investigated the association of kidney function with all-cause mortality across three age groups. Data from the Tokyo Centenarian Study, Japan Semi-supercentenarian Study, and Kawasaki Ageing and Wellbeing Project were analyzed in 1,918 participants with baseline serum creatinine measurements were included (median follow-up: 1,399 days). eGFR was calculated using creatinine and cystatin C according to the Japanese Society of Nephrology equation. Associations with mortality were assessed using Cox regression models, and standardized 3-year absolute risks were estimated. Lower cystatin C-based eGFR was consistently associated with higher mortality, whereas creatinine-based eGFR showed weaker associations. Prognostic thresholds for eGFR declined with advancing age-approximately 45, 30, and 15 mL/min/1.73 m² at ages 85-89, 100-104, and ≥ 105 years, respectively. The 3-year absolute risk difference (ARD) between the low and high eGFR groups was modest (≈10%) at ages 85-89 years, larger (≈30%) at 100-104 years, and attenuated at ≥ 105 years, where the 3-year mortality exceeded 80%. eGFR remained a prognostically relevant marker in very old individuals; however, the magnitude of ARDs varied by age-modest in the younger-old adults, larger in centenarians, and attenuated in semi- and supercentenarians-supporting the adoption of age-specific CKD thresholds.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8399-8412"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomic biomarkers as mediators for the associations between frailty phenotypes and chronic respiratory diseases.","authors":"Yujia Bao, Shenghao Yuan, Jiawei Gu, Chen Shen, Linli Chen, Yibin Zhou, Jinjun Ran","doi":"10.1007/s11357-026-02099-w","DOIUrl":"10.1007/s11357-026-02099-w","url":null,"abstract":"<p><p>Frailty, a hallmark of systemic vulnerability in aging populations, is increasingly recognized in the clinical management of chronic respiratory diseases (CRDs). Molecular mechanism underpinning the relationships remain insufficiently elucidated. This study hence aimed to investigate whether proteomic biomarkers-circulating plasma proteins reflecting systemic inflammation, metabolism, and tissue remodeling-are associated with CRDs and may serve as potential mediators of the observed links. We analyzed data from a population-based cohort of 22,802 adults with proteomic measurements. Frailty was assessed by three phenotypes, including frailty index, physical frailty, and psychological frailty. Related-proteomic signatures were estimated by both linear and elastic regression models. Cox regression models were applied to explore the associations of frailty phenotypes and their proteomic signatures with incident CRDs, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), as well as lung function outcomes, with full adjustments for potential confounders. Furthermore, mediation analyses were conducted to explore underlying mechanisms, complemented by pathway enrichment analyses to reveal relevant biological functions. Over a median follow-up of 13.2 years, 617 participants developed asthma, 701 developed COPD, and 228 developed IPF. Higher frailty index was associated with elevated risks of asthma (HR 1.95, 95% CI 1.64 to 2.31) and COPD (2.02, 1.71 to 2.38). Corresponding proteomic signature also related to increased risks of asthma (HR 1.22, 1.11 to 1.34) and COPD (1.65, 1.53 to 1.78). Mediation analysis suggested that the frailty index partially mediated the association with COPD, accounting for 26.0% (95% CI: 18.7 to 37.5%) of the total effect, respectively, particularly for GDF15, WFDC2, and PLAUR. Pathway enrichment analysis showed that these mediating proteins were predominantly involved in immune activation, inflammatory signaling, and metabolic stress responses. Frailty phenotypes contribute to elevated CRDs risks, partly through proteomic dysregulation in inflammatory and metabolic pathways.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8285-8298"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}